Improving X-ray crystallography modelling

In X-ray structure determination, the R-factor indicates how well a given model agrees with experimental data. The lower the percentage the more consistent is the model with the observed data.

When it comes to biological macromolecules, R-factors are high, highlighting the need for producing accurate models of macromolecular crystal structure. To address this, the EU-funded SOUPINMYCRYSTAL (How can we improve our models of biological macromolecules to reproduce experimental crystallographic X-ray intensities better?) project was initiated.

Structure determination stems from X-ray diffraction of the crystalline atoms into many specific directions. By measuring the angles and intensities of these diffracted beams, scientists produce a three-dimensional picture of the density of electrons within the crystal and reproduce a model of the crystallised molecule. However, macromolecular crystals contain large regions of disordered solvent – a soup of ions, buffers and water. All these contribute to the measured reflection intensities and possibly to a less accurate model.

First, researchers verified that neither the detector used to record the X-ray data nor the specific program used to refine the model affected structure determination. However, the solvent of macromolecular crystals generated significant scattering, and modelling of this behaviour produced R-factor improvements of up to 4 %. In addition, the consortium explored alternative quality indicators to the R-factor that are less dependent on overall crystal properties.

Collectively, the activities of the SOUPINMYCRYSTAL project are expected to produce better macromolecule models and more reliable biological conclusions. In particular, the structure determination of membrane proteins and large macromolecular complexes will not be hampered by low resolution data.